Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: Faster is better than more. More is better than less.

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Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: Faster is better than more. More is better than less.

Type: Doctoral Thesis
Title: Allogeneic haematopoietic stem cell donation and transplantation across the MHC class I barrier: Faster is better than more. More is better than less.
Author: Heemskerk, Martin Bartholomeus Alexander
Publisher: Department of Immunohematology and Blood Transfusion, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2006-09-28
Keywords: Unrelated donor
CD8+ T cell
Alloreactivity
Thymic selection
HLA
Mismatch
CTLp assay
HistoCheck
HLAMatchmaker
Abstract: Many patients in need of haematopoietic stem cell transplantation do not reach transplantation. An analysis on all unrelated donor searches for Dutch patients performed between 1987 and 2000 showed a significant decrease of the percentage of patients for whom no donor was available. Between 1996 and 2000, the efficiency of the donor search and transplantation process was the biggest constraint for patients of Northwest European origin. Thirty percent of patients became medically unfit for transplantation during the process, due to the duration of the process. Major Histocompatibility complex (MHC) differences between donor and patient can preclude successful transplantation. The assumption that highly diverged MHC class I molecules lead to more T cell alloreactivity was challenged. Single highly diverged (>=5alpha5beta) MHC class I molecules did not elicit an immune response by allogeneic CTL in vitro. I propose that in generating a T cell repertoire with a sufficiently narrow responsive for self-MHC, positive thymic selection limits the capacity to recognize allogeneic MHC molecules whose structure and sequence have diverged extensively. Its clinical relevance was evaluated. We could subdivide the donor-recipient pairs with a negative CTLp assay into a prognostic favourable and unfavourable group based on the (>=5alpha5beta) MHC mismatch category.
Description: Promotor: F.H.J. Claas, Co-Promotor: M. Oudshoorn
With Summary in Dutch
Faculty: LUMC
Citation: Heemskerk, M.B.A., 2006, Doctoral Thesis, Leiden University
ISBN: 9090209921
9789090209920
Sponsor: Jurriaanse stichting, Innogenetics, NRC (National Reference Center for Histocompatibility), Roche Pharmaceuticals, Novartis, Astellas, Bio-sys, Corning, Diamed, Dutch Transplantation Foundation
Handle: http://hdl.handle.net/1887/4578
 

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